Most physiological, biochemical and behavioral events in vertebrates, including man, show significant daily fluctuations. Importantly, these daily rhythms will continue under constant conditions, showing that they are driven by an internal "biological clock." Cycles in the environment, such as the daily light-dark cycle, synchronize internal rhythms so that the right internal events occur at the right time of day. The circadian system of man is important for maintaining health and well-being in at least three areas: (1) Abrupt changes in the temporal environment due to jet travel or shift work can cause disruptions of sleep, gastro-intestinal disturbances, and a general feeling of malaise. (2) Certain sleep disorders as well as mental illnesses, such as manic-depressive illness or seasonal depression, are believed to reflect inappropriate phase-relationships between internal daily rhythms. (3) The effectiveness of drug therapies, as well as the toxicity of drugs, varies with time-of-day. The proposed studies are designed to elucidate the physiology of the circadian system of a higher vertebrate, using the Japanese quail as a model. The sites which generate daily rhythms will be identified and the ways these areas communicate with each other (i.e., via neural or hormonal routes) will be examined. The routes by which light controls the circadian system will also be studied. These studies will focus on three areas which can act as biological clocks in vertebrates - the pineal organ, the suprachiasmatic nuclei of the hypothalamus, and the eyes. Various approaches will be used, including surgical manipulations such as SCN lesions and pinealectomy, and assessing the levels of a hormone, melatonin. Melatonin is produced by both the eyes and pineal and it is important in coordinating daily rhythms, at least in some verterbrates. The studies will indicate how these areas interact to produce a temporally adapted whole.